A High Density SNP Array for the Domestic Horse and Extant Perissodactyla: Utility for Association Mapping, Genetic Diversity, and Phylogeny Studies

PLoS Genetics, Jan 2012

An equine SNP genotyping array was developed and evaluated on a panel of samples representing 14 domestic horse breeds and 18 evolutionarily related species. More than 54,000 polymorphic SNPs provided an average inter-SNP spacing of ∼43 kb. The mean minor allele frequency across domestic horse breeds was 0.23, and the number of polymorphic SNPs within breeds ranged from 43,287 to 52,085. Genome-wide linkage disequilibrium (LD) in most breeds declined rapidly over the first 50–100 kb and reached background levels within 1–2 Mb. The extent of LD and the level of inbreeding were highest in the Thoroughbred and lowest in the Mongolian and Quarter Horse. Multidimensional scaling (MDS) analyses demonstrated the tight grouping of individuals within most breeds, close proximity of related breeds, and less tight grouping in admixed breeds. The close relationship between the Przewalski's Horse and the domestic horse was demonstrated by pair-wise genetic distance and MDS. Genotyping of other Perissodactyla (zebras, asses, tapirs, and rhinoceros) was variably successful, with call rates and the number of polymorphic loci varying across taxa. Parsimony analysis placed the modern horse as sister taxa to Equus przewalski. The utility of the SNP array in genome-wide association was confirmed by mapping the known recessive chestnut coat color locus (MC1R) and defining a conserved haplotype of ∼750 kb across all breeds. These results demonstrate the high quality of this SNP genotyping resource, its usefulness in diverse genome analyses of the horse, and potential use in related species.

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A High Density SNP Array for the Domestic Horse and Extant Perissodactyla: Utility for Association Mapping, Genetic Diversity, and Phylogeny Studies

and Phylogeny Studies. PLoS Genet 8(1): e1002451. doi:10.1371/journal.pgen.1002451 A High Density SNP Array for the Domestic Horse and Extant Perissodactyla: Utility for Association Mapping, Genetic Diversity, and Phylogeny Studies Molly E. McCue Danika L. Bannasch Jessica L. Petersen Jessica Gurr Ernie Bailey Matthew M. Binns Ottmar Distl Ge rard Gue rin Telhisa Hasegawa Emmeline W. Hill Tosso Leeb Gabriella Lindgren M. Cecilia T. Penedo Knut H. Red Oliver A. Ryder June E. Swinburne Teruaki Tozaki Stephanie J. Valberg Mark Vaudin Kerstin Lindblad-Toh Claire M. Wade James R. Mickelson Michel Georges, University of Lie`ge, Belgium An equine SNP genotyping array was developed and evaluated on a panel of samples representing 14 domestic horse breeds and 18 evolutionarily related species. More than 54,000 polymorphic SNPs provided an average inter-SNP spacing of ,43 kb. The mean minor allele frequency across domestic horse breeds was 0.23, and the number of polymorphic SNPs within breeds ranged from 43,287 to 52,085. Genome-wide linkage disequilibrium (LD) in most breeds declined rapidly over the first 50-100 kb and reached background levels within 1-2 Mb. The extent of LD and the level of inbreeding were highest in the Thoroughbred and lowest in the Mongolian and Quarter Horse. Multidimensional scaling (MDS) analyses demonstrated the tight grouping of individuals within most breeds, close proximity of related breeds, and less tight grouping in admixed breeds. The close relationship between the Przewalski's Horse and the domestic horse was demonstrated by pair-wise genetic distance and MDS. Genotyping of other Perissodactyla (zebras, asses, tapirs, and rhinoceros) was variably successful, with call rates and the number of polymorphic loci varying across taxa. Parsimony analysis placed the modern horse as sister taxa to Equus przewalski. The utility of the SNP array in genome-wide association was confirmed by mapping the known recessive chestnut coat color locus (MC1R) and defining a conserved haplotype of ,750 kb across all breeds. These results demonstrate the high quality of this SNP genotyping resource, its usefulness in diverse genome analyses of the horse, and potential use in related species. - Funding: The authors wish to acknowledge the following sources of funding: NIH NIAMS 1K08AR055713-01A2 to MEM, USDA CSREES 2008-35205-18766 to JRM, Morris Animal Foundation D07EQ-500 to JRM, Science Foundation Ireland PIYRA [04-YI1- B539] to EWH, EURYI award to KL-T, Haras Nationaux to GG, Horse Betting Levy Board and Thoroughbred Breeders Association to JES and MV, and Volkswagen Foundation, Hannover, Germany to OD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. . These authors contributed equally to this work. Horses have held a valued place in human civilization for over 5,000 years through service in war, agriculture, sport and companionship [1]. Over the last several centuries, more than 400 distinct horse breeds have been established by genetic selection for a wide number of desirable phenotypic traits [2]. In contrast to other large domestic animal species including cattle, chickens, sheep, swine, goats and camelids that are selectively bred mainly for production of food (meat, milk, eggs) or fiber, the domestic horse is primarily a utilitarian animal - bred for endurance, strength, speed, and metabolic efficiency [1]. The horses use as a work animal and We utilized the previously generated horse genome sequence and a large SNP database to design an ,54,000 SNP assay for use in the domestic horse and related species. The utility of this SNP array was demonstrated through genome-wide linkage disequilibrium, inbreeding and genetic distance measurements within breeds, as well as multidimensional scaling and parsimony analysis. Association mapping confirmed a large conserved segment containing the chestnut coat color locus in domestic horses. We also assess the utility of the SNP array in related species, including the Przewalskis Horse, zebras, asses, tapirs, and rhinoceros. This SNP genotyping tool will facilitate many genetics applications in equids, including identification of genes for health and performance traits, and compelling studies of the origins of the domestic horse, diversity within breeds, and evolutionary relationships among related species. means of transport required selection for individuals that were able to perform daily physical activity even when feedstuffs were scarce. The natural athleticism of horses and their enforced intensive exercise regimes makes them outstanding models for study of the musculoskeletal, cardiovascular and respiratory systems, while their natural susceptibility and resistance to infectious agents is useful in studies of the immune system. Understanding the genetic basis for within and among breed (...truncated)


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Molly E. McCue, Danika L. Bannasch, Jessica L. Petersen, Jessica Gurr, Ernie Bailey, Matthew M. Binns, Ottmar Distl, Gérard Guérin, Telhisa Hasegawa, Emmeline W. Hill, Tosso Leeb, Gabriella Lindgren, M. Cecilia T. Penedo, Knut H. Røed, Oliver A. Ryder, June E. Swinburne, Teruaki Tozaki, Stephanie J. Valberg, Mark Vaudin, Kerstin Lindblad-Toh, Claire M. Wade, James R. Mickelson. A High Density SNP Array for the Domestic Horse and Extant Perissodactyla: Utility for Association Mapping, Genetic Diversity, and Phylogeny Studies, PLoS Genetics, 2012, Volume 8, Issue 1, DOI: 10.1371/journal.pgen.1002451